CFHR3 Gene - Complement Factor H Related 3
A key regulator of complement activation and associated with renal and ocular diseases
Gene Information Card
| Symbol | CFHR3 |
|---|---|
| Full Name | Complement Factor H Related 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q31.3 |
| NCBI Gene ID | 10878 ncbi.nlm.nih.gov/gene/10878 |
| Ensembl ID | ENSG00000116785 |
| UniProt ID | Q02985 |
| OMIM ID | 605336 |
| HGNC ID | 4883 |
| Aliases | CFHL3, FHR3, HLF4 |
Description
The CFHR3 gene encodes complement factor H-related protein 3 (FHR-3), a member of the complement factor H protein family. FHR-3 is a secreted glycoprotein that modulates the alternative pathway of complement activation by competing with factor H for binding to C3b and microbial surfaces. It plays a role in immune surveillance and inflammation. Genetic variations in CFHR3, including copy number variations and deletions, are associated with susceptibility to age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and C3 glomerulopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Age-related macular degeneration (AMD) | CFHR3 deletion (delCFHR3-CFHR1) reduces complement regulation on retinal surfaces, increasing inflammation and drusen formation | PMID: 17053108, 20385826 |
| Atypical hemolytic uremic syndrome (aHUS) | CFHR3 mutations or hybrid genes disrupt complement control on endothelial cells, leading to microvascular thrombosis | PMID: 17634419, 23307826 |
| C3 glomerulopathy | CFHR3 gene rearrangements (e.g., CFHR3-CFHR1 fusion) cause uncontrolled complement activation and C3 deposition in glomeruli | PMID: 22549409, 24029273 |
| IgA nephropathy | CFHR3 deletion influences complement activation and disease progression | PMID: 21849964 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Plasma | N/A | Secreted |
| Kidney | 3.2 | Low |
| Retina | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.0 | Hepatocyte cell line |
| ARPE-19 | 2.5 | Retinal pigment epithelial cells |
| HK-2 | 1.0 | Kidney proximal tubule cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| delCFHR3-CFHR1 | Deletion | Common (allele frequency ~0.15 in Europeans) | Loss of CFHR3 and CFHR1; associated with reduced AMD risk but increased aHUS risk |
| c.481C>T (p.Arg161*) | Nonsense | Rare | Premature stop; loss of function; linked to aHUS |
| c.824G>A (p.Arg275Gln) | Missense | Rare | Altered C3b binding; potential gain-of-function in complement regulation |
Mutation functional classification
Loss of Function (LOF)
Deletion of CFHR3 (delCFHR3-CFHR1) leads to loss of FHR-3 protein, reducing competition with factor H and increasing complement activation on surfaces.
Gain of Function (GOF)
Missense mutations like p.Arg275Gln may enhance C3b binding, leading to excessive complement inhibition and immune evasion.
Dominant Negative (DN)
Hybrid genes (e.g., CFHR3-CFHR1) produce aberrant proteins that interfere with normal factor H and FHR function, causing dysregulated complement.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Complement and coagulation cascades (KEGG: hsa04610)
• Alternative complement pathway (Reactome: R-HSA-173736)
Protein Summary
Complement factor H-related protein 3 (FHR-3) is a 42 kDa secreted glycoprotein composed of five short consensus repeat (SCR) domains. It shares high sequence homology with complement factor H (CFH) but lacks the C-terminal regulatory domains. FHR-3 binds to C3b and microbial surfaces, competing with CFH and modulating complement activation. It is primarily produced in the liver and circulates in plasma. FHR-3 plays a role in immune evasion of pathogens and is implicated in complement-mediated diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CFHR3 Knockout HEK293 Cell Line | EDJ-KQ51013 | Human | 10878 | Details Get a Quote |
| CFHR3 Knockout HeLa Cell Line | EDJ-KQ55510 | Human | 10878 | Details Get a Quote |
| CFHR3 Knockout A-549 Cell Line | EDJ-KQ64000 | Human | 10878 | Details Get a Quote |
| CFHR3 Knockout HCT 116 Cell Line | EDJ-KQ72451 | Human | 10878 | Details Get a Quote |
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